Balancing Scaffold Degradation and Neo-Tissue Formation in In Situ Tissue Engineered Vascular Grafts.

An essential aspect of cardiovascular in situ tissue engineering (TE) is to ensure balance between scaffold degradation and neo-tissue formation. We evaluated the rate of degradation and neo-tissue formation of three electrospun supramolecular bisurea-based biodegradable scaffolds that differ in their soft-block backbone compositions only. Scaffolds were implanted as interposition grafts in the abdominal aorta in rats, and evaluated at different time points (t = 1, 6, 12, 24, and 40 weeks) on function, tissue formation, strength, and scaffold degradation. The fully carbonate-based biomaterial showed minor degradation after 40 weeks in vivo, whereas the other two ester-containing biomaterials showed (near) complete degradation within 6-12 weeks. Local dilatation was only observed in these faster degrading scaffolds. All materials showed to some extent mineralization, at early as well as late time points. Histological evaluation showed equal and non-native-like neo-tissue formation after total degradation. The fully carbonate-based scaffolds lagged in neo-tissue formation, presumably as its degradation was (far from) complete at 40 weeks. A significant difference in vessel wall contrast enhancement was observed by magnetic resonance imaging between grafts with total compared with minimal-degraded scaffolds.

Helical self-assembly and co-assembly of fluorinated, preorganized discotics.

The synthesis and self-assembly properties of a fluorinated C(3)-symmetrical 3,3'-bis(acylamino)-2,2'-bipyridine discotic (1) in the mesophase and in solution are described. First, 3,4,5-tris-(1H,1H,2H,2H,3H,3H-perfluoroundecyl-1-oxy)benzoyl chloride was coupled to mono-t-BOC protected 2,2'-bipyridine-3,3'-diamine to afford after deprotection the corresponding fluorinated aromatic amine on a multigram scale. Then, three-fold reaction of this amine with trimesyl chloride yielded the target C(3)-symmetrical fluorinated disc. The latter displayed columnar liquid crystallinity over a temperature range of more than 350 K in which helical rectangular and hexagonal columnar mesophases were detected by X-ray diffraction measurements. (1)H-NMR spectroscopy showed a preorganized structure due to strong intramolecular hydrogen bonding between the amide N-H's and bipyridine nitrogen atoms, even in the presence of a large excess of hexafluoroisopropanol. This preorganized structure allows the formation of helical self-assemblies in fluorinated solvents, as was established using UV-Vis spectroscopy. The fluorinated disc and two chiral hydrocarbon analogues (a C(3)-symmetrical and a desymmetrized disc) were mixed in a 1:10 v:v mixture of methoxynonafluorobutane (MNFB) and 1,1,2-trichloro-1,2,2-trifluoroethane (Freon 113). Importantly, the C(3)-symmetrical hydrocarbon disc dissolves only in the presence of fluorinated disc in the latter solvent mixture, proving a mutual interaction. CD spectroscopy performed on these mixtures points to a preference for alternating self-assemblies of fluorinated and chiral hydrocarbon discotics.

Desymmetrization of 3,3'-bis(acylamino)-2,2'-bipyridine-based discotics: the high fidelity of their self-assembly behavior in the liquid-crystalline state and in solution.

Two novel nonsymmetrical disc-shaped molecules 1 and 2 based on 3,3'-bis(acylamino)-2,2'-bipyridine units were synthesized by means of a statistical approach. Discotic 1 possesses six chiral dihydrocitronellyl tails and one peripheral phenyl group, whereas discotic 2 possesses six linear dodecyloxy tails and one peripheral pyridyl group. Preorganization by strong intramolecular hydrogen bonding and subsequent aromatic interactions induce self-assembly of the discotics. Liquid crystallinity of 1 and 2 was determined with the aid of polarized optical microscopy, differential scanning calorimetry, and X-ray diffraction. Two columnar rectangular mesophases (Col(r)) have been identified, whereas for C(3)-symmetrical derivatives only one Col(r) mesophase has been found. In solution, the molecularly dissolved state in chloroform was studied with (1)H NMR spectroscopy, whereas the self-assembled state in apolar solution was examined with optical spectroscopy. Remarkably, these desymmetrized discotics, which lack one aliphatic wedge, behave similar to the symmetric parent compound. To prove that the stacking behavior of discotics 1 and 2 is similar to that of reported C(3)-symmetrical derivatives, a mixing experiment of chiral 1 with C(3)-symmetrical 13 has been undertaken; it has shown that they indeed belong to one type of self-assembly. This helical J-type self-assembly was further confirmed with UV/Vis and photoluminescence (PL) spectroscopy. Eventually, disc 2, functionalized with a hydrogen-bonding acceptor moiety, might perform secondary interactions with molecules such as acids.

Chiral poly(ureidophthalimide) foldamers in water.

Poly(ureidophthalimide)s decorated with hydrophilic side chains, that ensure solubility in aqueous media, have been synthesized and characterized by UV/Vis and circular dichroism (CD) spectroscopy. Temperature and concentration dependent CD measurements in water have revealed an almost temperature and concentration independent Cotton effect, indicative for a strong intramolecular organization. Similar studies in THF demonstrate the dynamic nature of the secondary architecture, a characteristic of foldamers. In addition, the bisignated Cotton effect in water is opposite in sign to that in THF, suggestive for a solvent-dependent preference for one helical handedness. Mixing experiments prove the dominance of water in determining the handedness of the helical architecture. The solvent allows for control over the helical architecture and thus governs the supramolecular synthesis.

Radical cation formation in characterization of novel C3-symmetric disks and their precursors by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.

Four C3-symmetrical tris(dipeptide) disks and their precursors were characterized using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI TOF MS). The C3-symmetrical disks were based on a benzene-1,3,5-triscarboxamide core extended by oligopeptides with trialkoxyanilide tails. The results indicate that MALDI TOF MS is a powerful and straightforward analytical technique for characterizing C3-symmetrical disks and their precursors. Clear (pseudo)-molecular ion peaks could readily be identified. It is remarkable that strong radical ion signals were observed for all the compounds, including the anilines that were expected to be protonated prior to laser irradiation using acidic MALDI matrixes. Possible mechanisms for radical ion formation were investigated with the employment of radical scavengers, with various matrixes and with direct laser desorption/ionization (LDI). Most likely the radicals are formed by losing one electron from the aniline nitrogen and stabilized by conjugation through the phenyl ring. It appears that direct photo/thermal ionization of analytes is an important route for the radical ion formation of the compounds with trialkoxy aniline/anilide groups.

Synthesis of 3,6-diaminophthalimides for ureidophthalimide-based foldamers.

[reaction: see text]. Herein, we report an improved methodology for the synthesis of a variety of 3,6-diaminophthalimides in high yields. This enables decoration of the periphery of foldamers with a wide range of functionalities.